Éditeur(s) : HAL CCSD Landes Bioscience
Résumé : International audience
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
Autophagy

hal-00735751
https://hal.archives-ouvertes.fr/hal-00735751
PUBMED : 22966490

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Prostate cancer disparities have been reported in men of African descent who show the highest incidence, mortality, compared with other ethnic groups. Few studies have explored the genetic and environmental factors for prostate cancer in men of African ancestry. The glutathione-S-transferases family conjugates carcinogens before their excretion and is expressed in prostate tissue. This study addressed the role of GSTM1 and GSTT1 deletions on prostate cancer risk in populations of African descent. This multi-institutional case-control study gathered data from the Genetic Susceptibility to Environmental Carcinogens (GSEC) database, the African-Caribbean Cancer Consortium (AC3) and Men of African Descent and Carcinoma of the Prostate Consortium (MADCaP). The analysis included 10 studies (1715 cases and 2363 controls), five in African-Americans, three in African-Caribbean and two in African men. Both the GSTM1 and the GSTT1 deletions showed significant inverse associations with prostate cancer [odds ratio (OR): 0.90, 95% confidence interval (CI) 0.83-0.97 and OR 0.88, 95% CI: 0.82-0.96, respectively]. The association was restricted to Caribbean and African populations. A significant positive association was observed between GSTM1 deletion and prostate cancer in smokers in African-American studies (OR: 1.28, 95% CI: 1.01-1.56), whereas a reduced risk was observed in never-smokers (OR: 0.66, 95% CI: 0.46-0.95). The risk of prostate cancer increased across quartiles of pack-years among subjects carrying the deletion of GSTM1 but not among subjects carrying a functional GSTM1. Gene-environment interaction between smoking and GSTM1 may be involved in the etiology of prostate cancer in populations of African descent.
ISSN: 0143-3334

hal-00682901
https://hal.archives-ouvertes.fr/hal-00682901
DOI : 10.1093/carcin/bgr119
PUBMED : 21705483

Éditeur(s) : HAL CCSD American Association for the Advancement of Science
Résumé : 6 pages
International audience
Large impacts provide a mechanism for resurfacing planets through mixing near-surface rocks with deeper material. Central peaks are formed from the dynamic uplift of rocks during crater formation. As crater size increases, central peaks transition to peak rings. Without samples, debate surrounds the mechanics of peak-ring formation and their depth of origin. Chicxulub is the only known impact structure on Earth with an unequivocal peak ring, but it is buried and only accessible through drilling. Expedition 364 sampled the Chicxulub peak ring, which we found was formed from uplifted, fractured, shocked, felsic basement rocks. The peak-ring rocks are cross-cut by dikes and shear zones and have an unusually low density and seismic velocity. Large impacts therefore generate vertical fluxes and increase porosity in planetary crust.
ISSN: 0036-8075

hal-01399386
https://hal.archives-ouvertes.fr/hal-01399386
PUBMED : 27856906
DOI : 10.1126/science.aah6561

Éditeur(s) : HAL CCSD Elsevier
Résumé : This contribution reports our preliminary work to determine Cu isotope ratios for various granite rocks and examine the Cu isotope systematics within granite suites. A chemical procedure, modified from Marechal [Marechal, C.N., Telouk, R and Albarede, F., 1999. Precise analysis of copper and zinc isotopic compositions by plasma-source mass spectrometry. Chemical Geology, 156(1-4): 251-273.], Was used to separate Cu from rock matrix. Quantitative recovery (100.6 +/- 1.6%), with a low total procedural blank (2.65 +/- 0.66 ng) for Cu, has been achieved, allowing Cu isotopic measurements on samples with as little as 10 ppm Cu. The Cu isotope ratios (delta Cu-65 relative to NIST SRM 976) of 32 rock samples, ranging from mafic to felsic compositions, from 3 batholiths (2 I-type, 1 S-type) from the Lachlan Fold Belt in southeastern Australia. vary from -0.46 parts per thousand to 1.51 parts per thousand. Most of them cluster around zero, With mean values for the I-type and S-type granites of 0.03 +/- 0.15 parts per thousand and - 0.03 +/- 0.42 parts per thousand (2 sigma) respectively. These data, together with Cu isotope ratios of two loess samples, provide preliminary evidence that the baseline Cu isotopic composition of the crystalline part of upper continental crust is close to zero. The tight clustering of Cu isotope ratios of rocks from the I-type suites Suggests that high-temperature magmatic processes do not produce significant Cu isotope fractionation. However, two granites with abnormally heavy Cu isotope signatures (up to 1.51 parts per thousand) appears to be the result of localized hydrothermal alteration. Measurable variation in Cu isotopic composition of the S-type granite may reflect isotopic heterogeneity in the sedimentary Source region as a result of redox processes or may be due to hydrothermal overprinting. Thus, Cu isotope geochemistry may be a useful tracer for studying hydrothermal alteration and Source heterogeneity of granitic rocks.
ISSN: 0009-2541

hal-00413130
https://hal.archives-ouvertes.fr/hal-00413130
DOI : 10.1016/j.chemgeo.2008.06.047

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : Modern geochronology has moved beyond the acquisition of dates: the goal is to understand the significance of these numbers for the geodynamic evolution of Earth at all scales. The coupling of the laser-ablation microprobe (LAM) to inductively coupled plasma mass spectrometers (ICPMS, multicollector (MC)-ICPMS) has revolutionised geochronology and geochemistry over the last 10 years. These systems enable the rapid and precise in situ analysis of trace-element patterns and isotopic systems, while adding information related to microstructural context and major-element composition. The integration of these multiple sources of data is crucial in constraining the origin of the sample and the processes leading to its formation, so that we can understand the meaning of a date in terms of geological events. LAM-ICPMS measurement of U-Pb ages and trace-element patterns in zircon, coupled with LAM-MC-ICPMS analysis of Hf isotopes in the same grains, gives new insights into the processes of magma genesis. Applied to detrital zircons from modern drainages or sedimentary rocks (the TerraneChron approach), it becomes a powerful tool to investigate problems of crustal evolution on scales ranging from single terranes to continents. The in situ analysis (LAM-MC-ICPMS) of Re-Os systematics in single grains of sulfides in mantle-derived peridotites has demonstrated that most mantle rocks contain several generations of Os-bearing sulfides; whole-rock analyses are mixtures reflecting multiple melting and metasomatic events in the lithospheric mantle. These deep-seated events are commonly mirrored in the crust; Os model-age spectra from xenolith suites show age 'peaks' that correspond to the ages of thermal/tectonic events in the overlying crust, suggesting strong linkages between crust and mantle. Integrated studies of the timing and nature of crustal and mantle events, using these techniques, will be important for understanding the large-scale dynamics of the Earth.
ISSN: 0812-0099

hal-00411328
https://hal.archives-ouvertes.fr/hal-00411328
DOI : 10.1080/08120090802097450